The General Research Center (GCRC) serves as the physical and intellectual focus for clinical research endeavors at the Mount Sinai School of Medicine (MSSM). For the past 32 years, the GCRC has provided the essential resource to: l) elucidate the pathophysiologic mechanisms of a variety of diseases and 2) to evaluate laboratory advances at the bedside by determining the safety and efficacy of new or improved modalities for their diagnosis, treatment and/or prevention. In addition, the GCRC is the primary training site for clinical investigators in the Physician/Scientist tradition. Continuation of this invaluable research and training resource will permit the accomplishment of on-going studies by investigators from a wide variety of clinical disciplines, e.g., Community Medicine, Geriatrics, Human Genetics, Medicine, Neoplastics, Neurology, Ob/Gyn, Ophthalmology, Pediatrics, Psychiatry, and Surgery. Efforts are continuously underway to further enhance the use of the GCRC research resources by recruiting new Investigators and high quality research protocols. Emphasis will be directed to recruit and coordinate protocols in three areas: l) molecular medicine and the development of molecular-based therapies, especially cellular and gene therapies; 2) research in AIDS directed to pathogenesis, treatment and prevention and 3) biologic psychiatry with emphasis on schizophrenia and Alzheimer's Disease. Examples of such research studies include: l) Development and/or evaluation of gene-product replacement therapies for lysosomal storage disease using recombinant enzyme replacement therapy in Fabry, Gaucher Type 1, and Niemann-Pick B diseases, 2) Elucidation of the molecular basis of phenotypic variation and the identification of genotype/phenotype correlations for several inherited disorders, 3) Molecular studies of the ALA-dehydratase polymorphism and genetic susceptibility to lead toxicity, 4) Development and evaluation of pharmacologic and gene therapy strategies to the treatment of genetic disorders, particularly sickle' cell disease, Niemann-Pick B disease, and Glanzmann's thrombasthenia, 5) Studies of the etiology and treatment of AIzheimer's disease and psychiatric disorders, 6) Evaluation of cellular therapy in Parkinson's disease by fetal nigral cell transplantation, and 7) Evaluation of various approaches for the treatment and prevention of AIDS. To facilitate these studies, the Core Laboratory will continue to provide molecular biology expertise and consultation and offer GCRC investigators a variety of services such as establishment of fibroblast and lymphoblast lines, DNA extraction, Southern and northern analyses and PCR-based assays for common mutations or polymorphisms, including the use of robotics to automate repetitive assays. In addition, the Core Laboratory will increase its capabilities as the Gene Therapy Assessment Laboratory in order to monitor cell and gene therapy endeavors by semi-quantative RT-PCR, in situ hybridization, and other gene and protein detection techniques. The proposed new directions and laboratory capabilities should provide the clinical research environment for the anticipated medical advances resulting from molecular revolution.